The Fourth Left Atrial Appendage Occlusion Study

Inclusion Criteria:

1. (a) Persistent or permanent atrial fibrillation OR (b) Paroxysmal atrialfibrillation in participants with a history of ischemic stroke or systemic embolism

2. Increased risk of stroke, defined as a CHA2DS2-VASc stroke risk score of ≥ 4. [Note:the acronym CHA2DS2-VASc stands for congestive heart failure, hypertension, age ≥75 (doubled), diabetes, stroke (doubled), vascular disease, age 65 to 74 and sexcategory (female).]

3. Treatment with oral anticoagulants (Vitamin K agonist or factor Xa inhibitor) for atleast 90 days prior to enrollment, AND no documented plan to discontinue treatmentwith oral anticoagulants for the expected duration of the trial.

Exclusion Criteria:

1. Age < 18 years

2. Current left atrial appendage thrombus

3. Prior left atrial appendage occlusion or removal (surgical or percutaneous)

4. Prior percutaneous atrial septal defect or patent foramen ovale closure

5. Prior atrial fibrillation ablation unless evidence of recurrent qualifying atrialfibrillation present at least 30 days following ablation

6. Planned atrial fibrillation ablation within 90 days of enrollment

7. Individuals being treated with direct thrombin inhibitors

8. Women of childbearing potential unless they agree to employ effective birth controlmethods throughout the study

9. Anticipated life-expectancy of < 2 years

10. Patient unable or willing to give informed consent